Various technologies exist in which parts of an animal or human body may be images so as to aid in diagnosis and therapy of medical disorders. Some of these existing techniques are described in this section.
X-ray is the most well-known imaging techniques to visualize skeletal and other internal structures within animals and humans. However, a number of problems associates with the use of X-rays. Firstly, X-ray is not a safe diagnostic method is visualizing some parts of the human body, the use of X-ray for some of the organs and blood vessels is unsatisfactory. In addition, X-ray is dangerous if the amount of exposure is excessive; further, all X-ray radiation absorbed over a lifetime is cumulative.
Another technique, radio-nuclide imaging involves the injection of radioactive substances, such as thallium into the bloodstream. This technique require the use of very expensive and sophisticated machinery. Further, radionuclide imaging produces images of only a limited number of view of the heart and those images may not be of exceptional clarity. Finally, this type of radiation is cumulative over a lifetime and this is hazardous.
Ultrasound imaging techniques is safe, cheap, relatively easy to operate and the image produced is in real-time. Therefore, ultrasound is widely used in diagnostic imaging nowadays. The basis for ultrasound imaging is that, ultrasonic waves are sent into human body by an ultrasound probe and the waves reflected from the tissues are detected by the same probe, the receive signal is then processed to produce images on a monitor by a ultrasonic diagnostic instrument. According to different acoustic properties of different tissues in the human body, the diagnosis of diseased tissues can be distinguished from normal tissues quickly by observing the real-time image produced on the monitor. In addition to diagnostic application, the visualization of blood flow is also a common application of ultrasound in medical imaging, by monitoring the change in frequency of ultrasonic waves sent to blood vessels and the reflected waves. The blood flow velocity can be calculated.
Since early ultrasound techniques suffered from a lack of clarity, extensive efforts were undertaken to improve the ultrasonic equipment. To deal with this problem, it is valuable to mention that when ultrasonic energy is directed through substances, changes in the substances' acoustic properties will be most prominent at the interface of different media (i.e. solids, liquids and gases). As a consequence, when ultrasound energy is directed through various media, the reflection of ultrasound at the interface of different media will be the strongest and can be detected most easily. That is the basic principle for the making of ultrasonic contrast agents.
Contrast agents were introduced into the bloodstream in an effort to obtain enhanced images. The maximum ultrasonic reflection that we can obtain is that from the interface between liquid and gaseous media. That is way many of these contrast agents were liquids containing microbubbles of gas. These contrast agents themselves are intense sound wave reflectors because of acoustic differences between the liquids and the gas microbubbles enclosed therein. When the contrast agents are injected into and perfuse the microvasculative to tissue, clearer images of such tissue may be produced. However, not withstanding the use of such contrast agents, the image produced, for example, of the myocardial tissue, is of relatively poor quality, is highly variable and is not quantifiable due to the variable size and persistence associated with prior art microbubbles.
In the recent years, much effort was made to manufacture microbubble type contrast agents which includes Albunex.RTM. by Widder et al and Lipid-Coated Microbubbles (LCM) by D'Arrigo. For the commercially existing ultrasonic contrast agent Albunex.RTM., although has a reported mean diameter under 6 .mu.m, up to 0.5% of the microbubbles, or up to 2,000,000 microbubbles/ml are over 9 .mu.m in diameter in the fully purified product. According to J. Ophir, the microbubbles which are above 3 to 5 .mu.m will not pass through the lung capillaries. Therefore, the microbubbles cannot reach the organs to provide diagnostic properties. In this sense, microbubbles sized below 5 .mu.m should be made in order to overcome this problem. Overcoming the problem of size, D'Arrigo successfully made Lipid-Coated Microbubbles (LCM) of which 99% of the microbubbles are sized below 4.5 .mu.m in diameter by the use of surfactants. However, the number of microbubbles made in D'Arrigo's invention is much less than that of Albunex.RTM. which is in the order of 1.times.10.sup.8. The number of microbubbles made by D'Arrigo is in the order of 1.times.10.sup.6. For the best imaging properties to occur, it is desirable to have higher concentration of microbubbles. Furthermore, there is not yet a method or a effective way to control the size of the microbubbles produced which may suit different conditions for other commercial uses.